4.7 Article

Robust identification of temporal biomarkers in longitudinal omics studies

Journal

BIOINFORMATICS
Volume 38, Issue 15, Pages 3802-3811

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/bioinformatics/btac403

Keywords

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Funding

  1. NIH Common Fund Human Microbiome Project (HMP) [1U54DE02378901]
  2. NIH [S10OD020141]
  3. Stanford Clinical and Translational Science Award [UL1TR001085]
  4. Diabetes Genomics and Analysis Core of the Stanford Diabetes Research Center [P30DK116074]

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This study developed a statistical method called OmicsLonDA that robustly identifies time intervals of temporal omics biomarkers. The method uses a semi-parametric approach to model longitudinal data and infer significant time intervals based on an empirical distribution. Through testing on simulated datasets and real datasets, the method demonstrated high accuracy and sensitivity.
Motivation Longitudinal studies increasingly collect rich 'omics' data sampled frequently over time and across large cohorts to capture dynamic health fluctuations and disease transitions. However, the generation of longitudinal omics data has preceded the development of analysis tools that can efficiently extract insights from such data. In particular, there is a need for statistical frameworks that can identify not only which omics features are differentially regulated between groups but also over what time intervals. Additionally, longitudinal omics data may have inconsistencies, including non-uniform sampling intervals, missing data points, subject dropout and differing numbers of samples per subject. Results In this work, we developed OmicsLonDA, a statistical method that provides robust identification of time intervals of temporal omics biomarkers. OmicsLonDA is based on a semi-parametric approach, in which we use smoothing splines to model longitudinal data and infer significant time intervals of omics features based on an empirical distribution constructed through a permutation procedure. We benchmarked OmicsLonDA on five simulated datasets with diverse temporal patterns, and the method showed specificity greater than 0.99 and sensitivity greater than 0.87. Applying OmicsLonDA to the iPOP cohort revealed temporal patterns of genes, proteins, metabolites and microbes that are differentially regulated in male versus female subjects following a respiratory infection. In addition, we applied OmicsLonDA to a longitudinal multi-omics dataset of pregnant women with and without preeclampsia, and OmicsLonDA identified potential lipid markers that are temporally significantly different between the two groups.

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